Search

We investigated the molecular basis for a mild phenotype in a group of patients with β+thalassemia originating from Northern Sardinia by definition of the β-thalassemia mutation, a-globin mapping and β-globin haplotype determination. In nine patients, we detected the compound heterozygous state for the —87 promoter mutation and the codon 39 nonsense mutation; in one patient, we detected the combination of the codon 39 nonsense mutation and β+IVS-1 nt 6 mutation. These patients were either nontrans-fusion dependent for survival or became transfusion dependent later. We did not detect the —87 promoter mutation in any of 115 thalassemia major patients originating from the same part of Sardinia, investigated as controls. Heterozygotes for the —87 promoter mutation showed statistically higher hemoglobin (Hb) levels and larger and better hemoglobinized RBCs as compared with heterozygotes for the codon 39 nonsense mutation. From these data, we conclude that the —87 promoter mutation is a mild thalassemia allele, able to produce a phenotype of intermediate severity even in combination with a β°-thalas-semia mutant. The coinheritance of a-thalassemia or the — + + - -5’ subhaplotype in several cases may have contributed to development of the mild clinical picture. Characterization of the β-thalassemia mutation in combination with a-globin mapping and haplotype analysis may allow a better estimate of the probability of a given clinical phenotype, thus permitting more accurate counseling.